Men and women show partly distinct effects of physical activity on markers of brain integrity

Background Physical inactivity in older adults has been linked to an increased risk of dementia. On the other hand, increasing evidence indicates that sex is likely to influence Alzheimer’s disease (AD) pathophysiology, leading to a differential susceptibility to the disease in women versus men. We propose to investigate the interplay between sex and physical activity on brain integrity. Method We included baseline data of 134 cognitively unimpaired older adults (>65 years old, 82 women; Table) from the Age‐Well randomized control trial. They underwent multimodal neuroimaging, including structural MRI, FDG‐ and AV45‐PET, providing measures of grey matter volume (GMv), glucose metabolism, perfusion and Aβ burden. The Modifiable Activity Questionnaire was used to measure leisure time physical activity over the last 12 months. We assessed 1) the effect of sex on the amount of physical activity reported, 2) the main effects of sex and physical activity on each neuroimaging measure and 3) the interaction between sex and physical activity on the same variables. All analyses were controlled for age, education and APOE4 status. Result There was no sex differences in physical activity levels. GMv and brain perfusion in frontal medial regions were associated with both sex and physical activity, such that volume and perfusion were higher in women than in men and increased as a function of physical activity, without significant interaction between both terms. In contrast, there was an interaction between sex and physical activity on precuneus and posterior cingulate cortex perfusion and, at a trend level, on Aβ deposition (Figure). More specifically, the effect of physical activity on perfusion was stronger in women (higher activity being associated with higher perfusion), while its effect on amyloid burden was stronger in men (higher activity being associated with lower amyloid burden). Conclusion Our results suggest that physical activity has both sex‐dependent and sex‐independent effects on markers of brain integrity. Interestingly, the interaction between physical activity and biological sex suggests the existence of different reserve mechanisms in men and women, which might in turn influence their risk of AD.